This research is aimed at examining the potential use of lithium isotopes (6Li and 7Li) in the treatment and study of manic depressive illness. Particular attention will be paid to assessing the relative efficacy of one less toxic isotope, 7Li and natural lithium isotopic mixture in the treatment of the manic state and to their relative pharmacology, behavioral effects and toxicity during drug treatment. The absoprtion, excretion and body retention of both isotopes of natural lithium (6Li and 7Li) will also be examined during acute single dose administration of each isotope and appropriate studies will be performed to assess the behavioral effects and pharmacokinetics of each isotope. In addition studies of the rate of entry of the isotopes into red blood cells as a substitute for CNS neurons will be performed by appropriate in vivo and in vitro tests of transport of the isotope into and out of red blood cells. We want to ascertain if the minor isotope, 6Li, can be utilized as a tracer during pharmacological treatment with the major isotope, 7Li, thereby increasing our understanding of steady state kinetics of lithium during treatment. If our preliminary data is substantiated and the two isotopes are handled in a detectably differential manner by living systems, then these differences may provided a biological probe or marker which may allow identification of subgroups of manic depressive patients (i.e., lithium responders versus non-responders) or even identify in future studies those blood relatives of manic depressives with biological processes similar to the proband and thus suggestively at risk to develop the illness.